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Since the ASCO 2014 abstracts were released to the public on May 14, 2014 at 5:00pm EDT, the pre-meeting buzz in the press has been mostly about immunotherapies – specifically immunotherapies targeted against the immune checkpoint inhibitors Programmed (Cell) Death 1 (PD1) and its ligand (PDL1).  The late-stage investigational PD1/PDL1 antagonists pembrolizumab/MK-3475 (Merck), nivolumab (Ono/Bristol-Myers Squibb) and  MPDL3280A (Genentech/Roche) have garnered most of the pre-ASCO press and results of trials with several other early-stage PD1/PDL1 biologics, pidilizumab (Curetech), MEDI4736 (MedImmune/AstraZeneca), MSB-0010718C (Merck KGaA),  will also be presented at ASCO.

But what other immunotherapies warrant our attention at ASCO 2014?  Promising results from immunotherapies in early-stage clinical development from a diverse array of industry and academic sponsors and/or collaborations will be presented.  Many of these therapies have already advanced into later-stage clinical trials or will be evaluated in additional trials within the next year (1).  Highlighted below are the presentations from three types of immunotherapies.

Chimeric Antigen Receptor (CAR)-Engineered T Cells

  • Results will be presented from a phase I, Memorial Sloan-Kettering (MSK)-sponsored consolidation trial after purine analog-based treatment in patients with previously untreated chronic lymphocytic leukemia for CD19-targeted CAR+ T cells.  MSK, Fred Hutchinson Cancer Center, Seattle Children’s Research Institute are collaborating with Juno Therapeutics to develop CAR immunotherapies (Juno Therapeutics).
  • Another industry-academic medical center collaboration between Novartis and the Abramson Cancer Center at the University of Pennsylvania  will discuss the clinical development of CTL019, another CAR-engineered T cell immunotherapy targeting CD19 in two presentations at ASCO on Monday June 2, 2014:  “CTL019: Genetically Engineered T Cells and Beyond: Immune Modulation Therapy in Chronic Lymphocytic Leukemia” and “CTL019: Future Directions in Immune Targeting” (CTL019 ASCO presentations).  These investigators previously presented results from two trials for CTL019 at ASH 2013.
  • A third collaboration between the Surgery Branch of the National Cancer Institute Surgery and Kite Pharma will present results about a more efficient and rapid manufacturing process for the production of CAR-engineered T cells.  Using this improved process, initiation of a Kite-sponsored clinical trial in patients with aggressive non-Hodgkin’s lymphoma is expected in early 2015.

Oncolytic Viruses

  • The CALM trial in patients with advanced melanoma for Coxsackievirus A21/Cavatak
  • A first-in-class, first-in-human trial in patients with metastatic epithelial tumors for enadenotucirev, an oncolytic  Ad11/Ad3 chimeric group B adenovirus
  • The REO13 Brain trial of wild-type reovirus (pelareorep/Reolysin) infection of patients with brain tumors following intravenous administration

Antibody-Drug Conjugates

Presentations from phase I trials include:

  • DMOT4039A in patients with unresectable pancreatic or platinum-resistant ovarian cancers
  • DNIB0600A in patients with non-small cell lung or platinum-resistant ovarian cancers
  • DSTP3086S in patients with metastatic castration-resistant prostate cancer
  • IMGN529 in patients with relapsed or refractory non-Hodgkin’s lymphoma
  • IMGN853 in patients with epithelial ovarian cancer and other folate receptor alpha positive tumors
  • MLN0264 in patients with advanced gastrointestinal cancers
  • SGN-LIV1A in patients with LIV-1 positive breast cancer

Presentations from phase I/II and phase II trials include:

  • IMMU-130 in patients with metastatic colorectal cancer
  • IMMU-132 in patients with metastatic solid tumors
  • PSMA ADC in patients with taxane-refractory metastatic castration-resistant prostate cancer

Summary table of the highlighted immunotherapies

Drug Name Disease Target Trial Phase at ASCO Industry Developer Abstract
CAR-Engineered T Cells
CD19-targeted CAR+T cells CLL CD19 I Juno 7020
CTL019 ALL, CLL CD19 I, II Novartis
PG13-CD19-H3 transduced PBL/KTE-C19 CAR B cell lymphoma or leukemia CD19 I Kite 3079
Oncolytic Viruses
Cavatak/CVA-21 melanoma II Viralytics 3031
enadenotucirev epithelial solid tumors I PsiOxus 3103
pelareorep/Reolysin brain tumors I Oncolytics 3104
Antibody-Drug Conjugates
DMOT4039A pancreatic or ovarian cancers MSLN I Genentech 2529
DNIB0600A NSCLC or ovarian cancer NaPi2b (SLC34A2) I Genentech 2504
DSTP3086S prostate cancer STEAP-1 I Genentech 5024
IMGN529 NHL CD37 I ImmunoGen 8526
IMGN853 ovarian cancer or FRα positive solid tumors FRα I ImmunoGen 5571
MLN0264 gastrointestinal tumors GCC I Millennium 3546
SGN-LIV1A breast cancer LIV-1 I Seattle Genetics TPS1143
IMMU-130 colorectal cancer CEACAM5 I/II Immunomedics 3106
IMMU-132 solid tumors Trop-2 I/II Immunomedics 3032
PSMA ADC prostate cancer PSMA II Progenics 5023

 

So look past the frenzy about the anti-PD1 and anti-PDL1 biologics at ASCO 2014 and look at the presentations about other types of immunotherapies, namely CAR-engineered T cells, oncolytic viruses and antibody-drug conjugates.  Some of these early-stage immunotherapies could steal the show at ASCO 2015

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